Pharmacogenetics trials offer new challenges
Recruiting subjects is top concern
The brave new world of genetics and pharmacogenetics research provides some exciting possibilities as well as some major challenges to researchers.
For example, pharmacogenetics holds the possibility of identifying individuals who may obtain the greatest potential benefit from a particular drug and identifying individuals who may be at greatest risks for side effects from a particular drug, explains Barbara Handelin, PhD, chief executive officer of Kenna Technologies Inc. of West Chester, PA.
The Pharmacogenetics Working Group was formed to address the many common challenges associated with pharmacogenetics research, she notes. "The working group has representatives from 20-plus pharmaceutical companies who are engaged in various levels and degrees of studies," Handelin says.
One of the major challenges facing investigators and clinical trial administrators who are engaged in genetics or pharmacogenetics research is recruiting subjects because people often are concerned about their privacy with regard to genetic information.
When a trial is designed to provide the enrollee with the genetic information or when there is a way for the information to be linked back to the individual, it is not possible to guarantee that the information never could be put at risk of disclosure, genetics research experts say.
And any time such information is disclosed, there’s the potential that it will be used to discriminate against an individual, which is why those working in this industry have been in favor of legislation that would protect subjects from discrimination. One such bill, called the Genetic Information Nondiscrimination Act of 2003 was passed in the U.S. Senate and still is pending in the House of Representatives.
The bill would prohibit employers and health insurers from discriminating against people based on genetic information, says Laura Lyman Rodriguez, PhD, special advisor to the director of the National Human Genome Institute in Bethesda, MD.
"There have not been many cases of actual discrimination based on genetic information, but there is potential for it, and there is a great fear in the public in terms of this possibility," she says. "We’re hoping the [bill] can be proactive in keeping people from becoming afraid either for health reasons or for employment.
While the Health Insurance Portability and Accountability Act (HIPAA) provides for the privacy of health information, including information obtained during clinical trials, it doesn’t protect people against discrimination in the event that the information is accidentally released.
"Presumably [genetic information] should be anonymous and shouldn’t get out," Rodriguez says. "But there are no protections in place with regard to nondiscrimination."
A nondiscrimination law would ease potential research subjects’ minds and maybe make them more willing to participate, particularly in trials where the genetic information will be used in assessing health outcomes, she adds.
"We want to encourage participation in genetic research since more and more genetic aspects are included into protocols," Rodriguez says. "And if people are afraid that this information could get out and be used against them in some fashion, then they might not join a study, and we don’t want that to happen."
The public’s fear of disclosure of private medical information is well founded, says Mark A. Rothstein, JD, director of the Bioethics Institute at the University of Louisville (KY) School of Medicine.
"All medical records should be subject to stringent safeguards, which we currently do not have, and our attempts to do so have been totally wrong-headed," he says. "The reason there is not anything relevant in place is because third parties can make a condition upon signing of a release an authorization of disclosure of all medical records in an individual’s file, so there’s no protection."
While some states have laws that protect against the dissemination of genetic information, those laws do not prohibit an employer from gaining access to medical information, including genetic information, Rothstein explains.
"So the problem isn’t that numerous companies are discriminating; the problem is that people are dissuaded from taking genetic tests because they think their employers are going to have access to the information," he says. "Laws prohibiting discrimination don’t have an impact on access."
On the other hand, researchers sometimes are so afraid of having too few people enroll in their genetics studies that they will make the research anonymous and limit its power, Rothstein notes.
"It’s a very serious problem," he says. "I’m constantly talking to researchers about the best way to do it and how to get the proper level of informed consent."
Access to information
Clinical trial administrators and researchers also need to decide the best way to give participants any outcomes or information resulting from genetic research, Handelin says.
"Is the principal investigator appropriately trained and experienced in explaining the testing and results of the genetic test, or do they have nurses or someone else who will give this information to families and patients?" she asks. "If this is a researcher who got into genetics because his favorite disease has a genetic component, then he may not be the right person to deliver this information."
Another issue that sometimes comes up during recruitment for a genetic protocol is the possibility of coercion by people other than the investigator and clinical trials team.
For instance, when investigators are conducting genotype specific research, they need to recruit individuals with specific known genotypes, Rothstein says.
Often, these individuals are known because of their family members’ participation in other genetic research regarding a specific disease, and sometimes one family member may attempt to coerce another into participation, he notes.
"You have an issue then of what role a referring physician should play and what inducements should be given to referring physicians or subjects for participating in the research," Rothstein says. "Also, what commercial interests are retained by researchers, and what rights, morally or ethically, should they have in the financial products."